Despite great progress over the past 50 years in reducing the rate of smoking, tobacco dependence remains a leading public health concern in the US. To ensure the sustained and impactful research effort dedicated to addressing tobacco dependence, rigorous and inter-disciplinary mentoring programs are needed to prepare the next generation of researchers committed to tobacco dependence patient-oriented research (POR). I have led a successful research program focused on the evaluation of methods to improve the use and effectiveness of treatments for nicotine dependence for ~20 years and, during this time, I have mentored 24 students, fellows, or junior faculty. This Mid-Career Investigator Award will be used to support 2 overarching career goals. First, to support my primary mentorship career goal, I will formalize and enhance the mentoring activities that I have been engaged in since 2001 into a structured, comprehensive, and impactful mentoring program in tobacco dependence POR for students, fellows, and junior faculty. This will involve: 1) the implementation of a formal mentoring framework for trainees with different academic levels, which will double the number of mentees vs. the past 5 years and markedly increase mentoring productivity and impact in terms of publications and grants; 2) strengthening a pipeline for mentee recruitment through new mechanisms such as T32s and TCORS; and 3) the recruitment and mentoring of 6 students, 4 fellows, and 3 junior faculty over the next 5 years, in addition to 5 current mentees (for a total of 18). My mentoring program will use NIDA's mentoring framework, and will: 1) focus on students and junior faculty to ensure that training begins early in a mentee's career; 2) provide individualized training based on mentee's goals and abilities; 3) provide short/intensive and long/sustained traineeships depending on the mentee; 4) offer training in inter-disciplinary science; and 5) offer intensive training in patient-oriented research (POR). To facilitate my career development, I will: 1) use a Mentoring Advisory Committee, comprised of faculty experienced with mentoring, 2) complete courses, conferences, and workshops in translational and implementation science and mentoring and leadership; and 3) join a Penn effort to enhance links between behavioral and primary care. Second, to support my primary research career goal, I will broaden my POR program to include translational and implementation science through a pilot study of the use of the nicotine metabolite ratio (NMR) for promoting clinician prescribing and patient use of treatments for nicotine dependence within primary care. Based on our work showing that personalizing nicotine dependence treatment using the NMR improves treatment effectiveness and safety, the pilot will assess the translational potential of this model within primary care, while providing opportunities for mentee training and facilitating a subsequent R01. This mid-career investigator award will markedly improve my past mentoring record, offer new opportunities for mentoring and career development, and enable the expansion of my POR program to include translational and implementation science.